Renal Physiology 7 Renal Regulation of Body Fluid

(Renal Physiology 7) Renal Regulation of Body Fluid Ahmad Ahmeda aahmeda@ksu. edu. sa Cell phone: 0536313454 1

Learning Objectives: • Identify and describe the role of the Sensors and Effectors in the renal regulation of body fluid volume & osmolality • Describe the role of the kidney in regulation of body fluid volume & osmolality • Understand the role of ADH in the reabsorption of water and urea • Identify the site and describe the influence of aldosterone on reabsorption of Na+ in the late distal tubules. 2

The Composition of the Human Body: 3

Solute Overview: Intracellular vs. Extracellular • • • Ionic composition very different Total ionic concentration very similar Total osmotic concentrations virtually identical 4

The major body fluid compartment and membranes separate them 5

Regulation of volume & osmolality • Body water balance must be maintained. • Kidneys concentrate or dilute urine. • To remain properly hydrated, water intake must equal water output. • Increases in plasma osmolality trigger thirst and release of antidiuretic hormone (ADH) 6

Water Steady State: • Amount ingested = amount eliminated. • Pathological losses: – Vascular bleeding. – Vomiting. – Diarrhea. 7

Control of circulating volume • All down to Na+ balance i. e. absorption & excretion Volume sensors: (Effectively pressure receptors) a) Vascular: 1. Low pressure sensors: Cardiac atria (ANP), pulmonary vasculature. 2. High pressure: carotid sinus, aortic arch and juxtaglomerular apparatus of the kidney. b) Central nervous system. c) Hepatic. 8

Control of circulating volume • A) Volume sensor signals/Mediators: Neural: If pressure ↓ Renal sympathetics: a) afferent & Efferent arterioles constrict i) GRF ↓ ii) less Na+ filtred iii) more Na+ absorbed by PCT b) renin released i) ↑ aldosterone ii) ↑ angiotensin II 9

Control of circulating volume B) Hormonal: 1) Renin-angiotensin-aldosterone system ( pressure): • Renin secreted, by: a) Sympathetic stimulation b) perfusion pressure c) Na+ reaching macula densa • Angiotensin II: i) aldosterone release by adrenal cortex Na+ reabsorption in TAL, DT, CD ii) Vasoconstriction iii) ADH release iv) Na+ reabsorption in PCT 10

2) ANP: From atrial myocytes Released by stretch of atrium Na. Cl & water excretion Antagonist of renin-angiotensin: i) vasodilation of afferent arteriole, vasoconstriction of efferent i. e. GFR ii) renin release iii) direct aldosterone release iv) Na+ reabsorption in CD v) ADH release 11

Regulation of volume & osmolality • If water intake hypoosmotic urine dilute (~ 50 m. Osm/kg) large volume (up to 18 L/d!!) • If water intake hyperosmotic urine concentrated (up to 1200 m. Osm/kg) small volume (0. 5 L/d) • Renal water excretion mechanism(s) independent of solute excretion mechanism(s) allows water balance maintenance without damaging solute homeostasis (e. g. Na+, K+) 12

Antidiuretic hormone (ADH)/Vasopressin • It is synthesized in neuroendocrine cells located within the supraoptic and paraventricular nuclei of the hypothalamus • prevents water loss • small protein hormone (only 9 amino acids) • The synthesized hormone is • fast acting, short packaged in granules that are half life in transported down the axon of the cell circulation and stored in nerve terminals located • thirst in the neurohypophysis (posterior pituitary). 13

Antidiuretic hormone (ADH)/Vasopressin • Factors influencing release: Main physiological factors 1) Osmolality 2) Haemodynamic factors 3) Nausea → stimulates 4) Atrial natriuretic peptide (ANP) → inhibits 5) Angiotensin II → stimulates 14

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• A rough estimate of ECF osmolality can be obtained by doubling Plasma sodium concentration • 145 m. Eq/l X 2 = 290 (Normal 285 -295 m. Osm/kg H 2 O) ∴ Sodium concentration gives best estimate of effective osmolality of ECF. • In clinical situations glucose & urea concentrations (mmols) are also taken into account, useful in cases of patients with diabetes mellitus or chronic renal failure. • Neither glucose or urea are “effective osmoles” i. e. they do not shift fluid between ECF & ICF, • (non-absorbed glucose in kidney tubule can however prevent fluid absorption generating an osmotic diuresis). 16

Osmolality • Osmoreceptors in hypothalamus, outside blood-brain barrier. • osmolality ADH release • “set point” ~ 280 – 285 m. Osm/kg H 2 O 17

Blood volume • blood volume ADH release • less sensitive than osmolality • need 5 – 10% blood volume • As would be expected changes in blood volume affect osmolality • volume/BP set point steeper curve 18

ADH renal target • Collecting duct cells only permeable to water in presence of ADH • ADH causes in urea permeability in inner medullary CD • ADH stimulates reabsorption of Na. Cl by the thick ascending limb of Henle’s loop and by the DCT and cortical segment of CD 19

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Regulation of Water Intake • The hypothalamic thirst center is stimulated: – By a decline in plasma volume of 10%– 15% – By increases in plasma osmolality of 1– 2% – Via baroreceptor input, angiotensin II, and other stimuli. 21

Regulation of Water Intake • Thirst is quenched as soon as we begin to drink water • Feedback signals that inhibit the thirst centers include: – Moistening of the mucosa of the mouth and throat – Activation of stomach and intestinal stretch receptors 22

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Actions of Angiotensin II 1. Angiotensin II receptors are found on the zona glomerulosa cells of the adrenal cortex. • Activation of these receptors leads to an immediate and rapid increase in aldosterone secretion. • Aldosterone acts on the distal tubule and collecting duct to cause sodium retention. • This is likely to be an important mechanism for determining long-term sodium balance. 24

Actions of Angiotensin II 2. Vascular actions • Angiotensin II is one of the most potent vasoconstrictors known. • Constriction of vascular smooth muscle leads to a prompt rise in blood pressure. • It plays an important role in maintaining vascular tone and blood pressure in volume depleted states, for example haemorrhage and fluid depletion. 25

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